• Arch Med Sci · Jan 2023

    Dichloroacetate ameliorates myocardial ischemia-reperfusion injury via regulating autophagy and glucose homeostasis.

    • Shuo Li, Boqia Xie, Wenqian Zhang, and Tong Li.
    • Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
    • Arch Med Sci. 2023 Jan 1; 19 (2): 420429420-429.

    IntroductionAutophagy occurs in response to myocardial ischemia-reperfusion (I/R) injury and plays both a protective and detrimental role in this pathological process. Dichloroacetate (DCA) has a protective role during myocardial I/R injury, but its effects on autophagy induction are less well understood. We established a rat myocardial I/R injury model and investigated the effects of DCA on autophagy induction.Material And MethodsHealthy Sprague-Dawley (SD) rats were used to establish a myocardial I/R model. The effect of DCA on cardiac infarct size, cardiac function, and serum levels of serum creatine kinase (CK), lactic dehydrogenase (LDH) and cardiac troponin I (cTnI) during I/R injury were assessed. Using cultured rat cardiac myocytes, we investigated the functional implications of DCA and explored the relevant mechanism(s) of DCA protection during I/R injury.ResultsDCA significantly decreases infarct size and arrhythmia scores, increases heart rate (HR), left ventricular developed pressure (LVDP), the maximal rate of pressure rise (+dp/dtmax) and coronary flow (CF), and reduces the levels of CK, LDH and cTnI after I/R. DCA treatment enhanced myocardial cell viability and alleviated apoptosis assessed through TUNEL assays and Bcl-2/Bax expression. Notably, the levels of the autophagy biomarkers Beclin-1, LC3II and reactive oxygen species (ROS) significantly decreased following DCA treatment. When Bcl-2 was silenced, Beclin-1 expression significantly decreased following DCA treatment, suggesting that DCA confers a protective role during I/R injury through autophagy regulation. Moreover, DCA was found to regulate glucose homeostasis through increasing the expression of Glut-1 and Glut-4.ConclusionsDCA contributes to I/R injury protection through the regulation of autophagy and glucose homeostasis.Copyright: © 2019 Termedia & Banach.

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